Techniques to rapidly separate and detect different types of cells and other analytes of interest from biological samples are of interest in scientific research, the biotechnology industry and medicine. For example, fluorescence activated cell sorting (FACS) is now a conventional and standard methodology, but it requires very expensive equipment and is inherently limited by the serial nature of single cell optical sorting.
In another approach, particles within an acoustic channel can be separated from other components in a solution using acoustic force manipulation. See e.g., U.S. Pat. No. 7,340,957 issued Mar. 11, 2008, which is herein incorporated by reference in its entirety. Particles exposed to an ultrasonic standing wave field will experience an average drift force positioning them at local pressure potential minima within an acoustic radiation pressure force potential. See e.g., U.S. Patent Application Publication No. 2008/0245709, published Oct. 9, 2008, which is hereby incorporated by reference in its entirety. The ability of ultrasonic radiation to separate particles derives from the particles' density/compressibility ratio. The density/compressibility contrast between particles and their host medium will determine the positioning of the particles under acoustic radiation exposure. Positive acoustic contrast particles that have a density/compressibility ratio greater than the surrounding medium will be positioned at local pressure potential minima nodes along the center of the focusing chamber (focused). Conversely, negative acoustic contrast particles with a smaller density/compressibility ratio than the surrounding medium will be positioned at local pressure potential minima antinodes along the side of the focusing chamber. After this positioning, positive acoustic contrast particles can be removed from the acoustic focusing chamber, leaving behind only negative acoustic contrast particles which can subsequently be focused to the center of the chamber for analysis.
As described in the '709 patent application publication, most biological particles in aqueous solutions appear to exhibit positive acoustic contrast. Acoustic force manipulation has been used in the past to concentrate (focus) Chinese hamster cells, red blood cells, bacteria, fungal spores, and other types of biological particles in aqueous solution. See the '709 publication as well as Goddard, et al., Analytical Performance of an Ultrasonic Particle Focusing Flow Cytometer; Anal. Chem. (79), 8740-8746 (2007), which is incorporated by reference in its entirety. Exploiting this property, acoustic radiation can be used to trap elastomeric negative acoustic contrast particles (NACPs), and any analytes captured or engaged therewith, or separate them from many biological components within aqueous or unmodified biological samples. While the technology has improved, existing assays still suffer from the need for equipment that is not easily adapted to a point-of-care format.
Accordingly, there remains an unmet need for improved devices and methods for point-of-care assays to detect analytes in biological samples. The present disclosure provides such improved devices and methods.